Physicians diagnosing and treating disease involving inflammation of the joints, such as arthritis, including osteoarthritis (OA), rheumatoid arthritis (RA) or juvenile rheumatoid arthritis (JRA) have experienced difficulty in quantifying the extent of inflammation or establishing the diagnosis. A typical arthritis patient may present with one or more various symptoms relating to synovitis, including swelling, heat, redness and reduced mobility in one or more joints. However, it has proven remarkably difficult to measure these signs in arthritis patients in a consistent manner, or even to get agreement between rheumatologists as to the presence or absence of the disease in a given joint. Physician global assessment and assessment of swollen and/or tender joints are standard tools used to measure disease activity and response to therapy in clinical studies. Various components of these algorithms call for the unbiased, precise estimations of inflammation, as manifested by swelling, heat, erythema, pain on motion, tenderness and/or limitations of motion in the joints. Unfortunately, these measures are cumbersome, time-consuming, and often unreliable. Carefully designed studies have repeatedly shown poor reproducibility of these manifestations of synovitis. Both intra- and inter-rater reliability estimates show high coefficients of variations, and low correlation coefficients and intra-class correlations. Unfortunately, training workshops designed for “joint assessors” and conducted by experienced pediatric rheumatologists have had little impact in addressing this problem.
Partly because of the difficulty in accurately measuring joint inflammation, surrogate markers of inflammation and outcome measures for arthritis have been developed. As an example, the FDA and the American College of Rheumatology (ACR) have adopted the ACR 20/50/70 and the ACR Pediatric 30. These algorithms have gained widespread acceptance and are now used as the primary measure of response in both children and adults with inflammatory arthritis. The ACR algorithms include 6 core components: (1) physician global assessment of disease activity; (2) parent/patient assessment of overall well-being; (3) functional ability; (4) number of joints with active arthritis; (5) number of joints with limited range of motion; and (6) erythrocyte sedimentation rate (ESR), which is also included in the ACR 20/50/70. While components 1-3 require subjective assessments, either on the part of the patient or the physician, components 4-6 should be measurable and quantifiable. Tools that would produce a set of reliable, reproducible and objective measures of the inflammatory state of the joint would have at least two important benefits. First, they would improve assessment of outcome in clinical studies of arthritis by providing a more reliable measure of changes in synovitis in response to therapy. Second, they would be useful to the rheumatologist in the clinic by allowing objective comparison of a given patient's joints from visit to visit.
Improved objective measures of joint inflammation are clearly needed. Tools which could quantify the major components of the joint count assessment to develop a quantitative, highly reliable, time- and cost-efficient method of determining the major physical examination parameters of the joints would be highly desirable. Therefore, it is an object of this invention to develop tools for the objective measurement of various symptoms presented by arthritis patients.